title: Formation of STAT5/PPARgamma transcriptional complex modulates angiogenic cell bioavailability in diabetes.
abstract: OBJECTIVE
  Circulating angiogenic cells (CACs) expansion is a multistage process requiring sequential activation of transcriptional factors, including STAT5. STAT5, in concert with peroxisome proliferator-activated receptors (PPARs), seems to induce discrete biological responses in different tissues. In the present study we investigated the role of STAT5 and PPARgamma in regulating CAC expansion in normal and diabetic settings.
  
  
  RESULTS
  Normal and diabetic CACs were used. siRNA technology, EMSA, and chromatin immunoprecipitation (ChIP) assay as well as site-directed mutagenesis of the STAT5 response element in the PPARgamma promoter enabled us to demonstrate that STAT5 transcriptional activity controls PPARgamma expression. Moreover, FACS analysis, coimmunoprecipitation experiments, and ChIP assay revealed that a STAT5/PPARgamma transcriptional complex controls cyclin D1 expression and CAC progression into the cell-cycle. Conversely, PPARgamma agonists, by preventing the expression of STAT5 and the formation of the STAT5/PPARgamma heterodimeric complex failed to promote CAC expansion. Finally, we demonstrated that diabetic CAC functional capability can be recovered by molecules able to activate the STAT5/PPARgamma transcriptional complex.
  
  
  CONCLUSIONS
  Our data identify the STAT5/PPARgamma heterodimers as landmark of CAC expansion and provide evidences for a mechanism that partially rescues CAC bioavailability in diabetic setting.
authors.affiliation: Department of Internal Medicine, University of Torino, Corso Dogliotti 14, 10126, Torino, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Dentelli
authors.forename: Antonella
authors.initials: A
authors.lastname: Trombetta
authors.forename: Gabriele
authors.initials: G
authors.lastname: Togliatto
authors.forename: Annarita
authors.initials: A
authors.lastname: Zeoli
authors.forename: Arturo
authors.initials: A
authors.lastname: Rosso
authors.forename: Barbara
authors.initials: B
authors.lastname: Uberti
authors.forename: Francesca
authors.initials: F
authors.lastname: Orso
authors.forename: Daniela
authors.initials: D
authors.lastname: Taverna
authors.forename: Luigi
authors.initials: L
authors.lastname: Pegoraro
authors.forename: Maria Felice
authors.initials: MF
authors.lastname: Brizzi
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D009389:Neovascularization, Pathologic / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D047495:PPAR gamma; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050799:STAT5 Transcription Factor; D012313:RNA; D008156:Luciferases